Markers of tumor angiogenesis and proteolysis independently define high- and low-risk subsets of node-negative breast cancer patients.

Eppenberger, Urs; Kueng, Willy; Schlaeppi, Jean-Marc; Roesel, Johannes; Benz, Christopher C.; Mueller, Heinz; Matter, Andrea; Luescher, K; Litschgi, M; Foekens, J.; Eppenberger‐Castori, Serenella

doi:10.1200/jco.1998.16.9.3129

Cited by 208 publications

(124 citation statements)

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“…Further, VEGF is one of the most important factors in promoting neovascularization of breast tumours (Toi et al, 1996). The clinical prognostic value of VEGF has been substantiated by two recent studies that demonstrate that the level of VEGF 165 is a strong, independent prognostic determinant (Eppenberger et al, 1998;Linderholm et al, 1998).…”

mentioning

confidence: 88%

Production of VEGF and expression of the VEGF receptors Flt-1 and KDR in primary cultures of epithelial and stromal cells derived from breast tumours

Speirs

Atkin

1999

Br J Cancer

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Production of vascular endothelial growth factor (VEGF) and expression of its receptors Flt-1 and KDR was determined in primary cultures of separated epithelial and stromal-enriched cultures derived from ten primary human breast carcinomas. By enzyme-linked immunosorbent assay, epithelial cells produced a mean VEGF of 33 ± 7 pg ml −1 μg −1 RNA (range 11–70). Stromal cells produced similar levels, with a mean of 48 ± 11 pg ml −1 μg −1 RNA (range 7–92). This was significantly greater than the amount produced by similar cultures derived from normal breast tissue (epithelial mean 19 ± 5 pg ml −1 μg −1 RNA, range 9–34, P < 0.05 vs tumour epithelial culture; stromal mean 26 ± 8 pg ml −1 μg −1 RNA, range 3–56). Flt-1 and KDR receptors were analysed by semi-quantitative reverse transcription polymerase chain reaction. Flt-1 was expressed by four of six epithelial and five of six stromal cultures. When expressed by both cell types, Flt-1 appeared to be significantly more abundant on stromal cells compared with epithelial cultures. Only a single tumour, a lobular carcinoma, failed to express Flt-1 on either cell type. With KDR, the reverse was true with constitutive expression of this receptor by epithelial cultures and zero or reduced (3/6) expression by stromal cultures. Differences in the expression pattern of VEGF receptors may reflect a differential response to VEGF by specific cell types. Thus, production of VEGF and expression of VEGF receptors Flt-1 and KDR by breast cancer epithelial and stromal cells suggests that VEGF may fulfil not only an angiogenic role, but also play a fundamental role as an autocrine/paracrine regulator in breast cancer, thereby facilitating tumour proliferation and subsequent invasion. © 1999 Cancer Research Campaign

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mentioning

confidence: 88%

Production of VEGF and expression of the VEGF receptors Flt-1 and KDR in primary cultures of epithelial and stromal cells derived from breast tumours

Speirs

Atkin

1999

Br J Cancer

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“…With reference to the National Institutes of Health (28) and the St. Gallen consensus guidelines (29), up to 90% of LN-negative breast cancer patients are eligible to receive adjuvant systemic chemotherapy. By use of uPA and PAI-1 as additional prognostic factors, subgroups of LN-negative patients at high or low risk can be identified (30)(31)(32)(33)(34)(35)(36). Patients at high risk, as identified by elevated uPA and/or PAI-1 protein levels, benefit from adjuvant systemic chemotherapy, resulting in a substantial reduction of risk of relapse (1,31).…”

Section: Discussionmentioning

confidence: 99%

Quantitative RT-PCR assays for the determination of urokinase-type plasminogen activator and plasminogen activator inhibitor type 1 mRNA in primary tumor tissue of breast cancer patients: Comparison to antigen quantification by ELISA

Biermann

Holzscheiter²,

Kotzsch³

et al. 2008

Int J Mol Med

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Abstract. Urokinase-type plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor type 1 (PAI-1) play a key role in tumor-associated processes such as the degradation of extracellular matrix proteins, tissue remodeling, cell adhesion, migration, and invasion. High antigen levels of uPA and PAI-1 in tumor tissue of various solid malignant tumors, including breast cancer, are associated with poor patient prognosis. In the present study, we examined whether analysis of uPA and PAI-1 mRNA expression represents an alternative to the measurement of the respective antigen levels in breast cancer. Highly sensitive quantitative real-time PCR (QPCR) assays, based on the LightCycler technology, were established to quantify uPA and PAI-1 mRNA expression in breast cancer cell lines as well as in tumor tissue of breast cancer patients. mRNA concentrations were normalized to the expression level of the housekeeping gene h-G6PDH. The respective uPA and PAI-1 antigen concentrations were determined by established ELISA formats. QPCR mean interassay variation coefficients were 11% (uPA) and 8% (PAI-1). In breast cancer cell lines, mRNA and antigen values were highly correlated for both uPA and PAI-1 (each: r s =0.95; p<0.001). In contrast, correlations between uPA/PAI-1 mRNA and protein in the breast cancer samples were found to be distinctly weaker or not significant. Thus, quantitative determination of mRNA expression for both factors does not mirror antigen levels in breast cancer tissue, possibly due to posttranscriptional regulation. Except for nodal status being inversely correlated with uPA mRNA levels, no significant interrelations were observed between uPA or PAI-1 mRNA expression and clinicopathological parameters. On the protein level, elevated uPA and PAI-1 values were associated with a negative steroid hormone receptor status. In conclusion, the implementation of mRNA quantification of uPA and PAI-1 in breast tumors is unable to serve as a one-to-one substitution for antigen determination by ELISA.

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“…Increased tumor cell proliferation is accompanied by cell matrix remodeling and neo-angiogenesis, which together form the basis for an aggressive tumor phenotype (Ellis Eppenberger et al, 1998). Since tumors that exhibit increased proliferation tend to be more aggressive clinically, measures of proliferation are often incorporated into histological grading systems.…”

Section: Introductionmentioning

confidence: 99%

Ki67 Index in Breast Cancer: Correlation with Other Prognostic Markers and Potential in Pakistani Patients

Haroon¹,

Hashmi²,

Khurshid³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Markers of tumor angiogenesis and proteolysis independently define high- and low-risk subsets of node-negative breast cancer patients.

Abstract: Separate primary and validating clinical studies concur that tumor VEGF level is the most important prognostic parameter among several markers of tumor angiogenesis and proteolysis.

Cited by 208 publications

References 0 publications

Production of VEGF and expression of the VEGF receptors Flt-1 and KDR in primary cultures of epithelial and stromal cells derived from breast tumours

Production of VEGF and expression of the VEGF receptors Flt-1 and KDR in primary cultures of epithelial and stromal cells derived from breast tumours

Quantitative RT-PCR assays for the determination of urokinase-type plasminogen activator and plasminogen activator inhibitor type 1 mRNA in primary tumor tissue of breast cancer patients: Comparison to antigen quantification by ELISA

Ki67 Index in Breast Cancer: Correlation with Other Prognostic Markers and Potential in Pakistani Patients

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